title: Breath analysis in pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath.
  
  
  METHODS
  We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n=31) and from healthy control subjects (n=34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts.
  
  
  RESULTS
  Patients with PAH were 51.5±14 years old, and 27 were women (85%). Control subjects were 38±13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P<.001) and was associated with right atrial pressure (ρ=0.57, P<.001), mean pulmonary artery pressure (ρ=0.43, P=.015), cardiac index by thermodilution (ρ=-0.39, P=.03), pulmonary vascular resistance (ρ=0.40, P=.04), mixed venous oxygen (ρ=-0.59, P<.001), and right ventricular dilation (ρ=0.42, P=.03).
  
  
  CONCLUSIONS
  Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease.
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Cikach
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Adriano R
authors.initials: AR
authors.lastname: Tonelli
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Jarrod
authors.initials: J
authors.lastname: Barnes
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Kelly
authors.initials: K
authors.lastname: Paschke
authors.affiliation: Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Jennie
authors.initials: J
authors.lastname: Newman
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: David
authors.initials: D
authors.lastname: Grove
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Luma
authors.initials: L
authors.lastname: Dababneh
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH.
authors.forename: Sihe
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pathobiology Department, Lerner Research Institute, Cleveland Clinic, Cleveland, OH. Electronic address: dweikr@ccf.org.
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
mesh_terms: D000328:Adult; D000388:Air / Q000032:analysis*; D001944:Breath Tests / Q000379:methods; D006328:Cardiac Catheterization; D045853:Exhalation; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D014655:Vascular Resistance